Caffeine intake induces an alteration in human neutrophil A_2A adenosine receptors

Abstract.

Caffeine is the most widely used drug in the world and acts mainly through antagonism of the effects mediated by the adenosine receptor subtypes A₁, A_2A, A_2B and A₃. We determined whether repeated caffeine administration at different doses and for different periods of time (400 or 600 mg/day for 1 week and 400 mg/day for 2 weeks) alters human neutrophil A_2A adenosine receptor density and function. Saturation binding assays showed an increase in affinity (K_D) and density (B_max) of A_2A adenosine receptors after caffeine intake. These changes were accompanied by increases in cAMP accumulation and decreases in superoxide anion production after stimulation of the A_2A receptor subtype using the agonist 5′-N-ethylcarboxamidoadenosine (NECA). Binding and functional changes of A_2A receptors returned to baseline after 48 h of caffeine withdrawal. The findings are consistent with a potential anti-inflammatory effect of caffeine mediated by neutrophil A_2A receptors.